Vaccines

5 pages, 156 KB

Open AccessEditorial

Tuberculosis Vaccines: Multidimensional Exploration and Breakthroughs from Innovative Design to Evaluation Systems

by Wenping Gong and Ashok Aspatwar

Vaccines 2025, 13(12), 1199; https://doi.org/10.3390/vaccines13121199 (registering DOI) - 28 Nov 2025

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB) and remains a major global public health challenge [...] Full article

(This article belongs to the Special Issue Research Progress of New Tuberculosis Vaccines and Vaccine Design)

13 pages, 833 KB

Open AccessArticle

Safety and Cross-Neutralizing Immunity Against SARS-CoV-2 Omicron Sub-Variant After a Booster Dose with SOBERANA^® Plus in Children and Adolescents

by Dagmar García-Rivera, Meiby Rodríguez-González, Beatriz Paredes-Moreno, Rinaldo Puga-Gomez, Yariset Ricardo-Delgado, Carmen Valenzuela Silva, Sonsire Fernández-Castillo, Rocmira Pérez-Nicado, Laura Rodríguez-Noda, Darielys Santana-Mederos, Yanet Climent-Ruiz, Enrique Noa-Romero, Otto Cruz-Sui, Belinda Sánchez-Ramírez, Tays Hernández-García, Ariel Palenzuela-Diaz, Yury Valdés-Balbín and Vicente G. Vérez-Bencomo

Vaccines 2025, 13(12), 1198; https://doi.org/10.3390/vaccines13121198 - 27 Nov 2025

Abstract

Background: With the emergence of SARS-CoV-2 Omicron sub-variants exhibiting increased transmissibility and immune escape, booster immunization is recommended. Ideally, vaccination across all age groups, including children and adolescents, is critical to control viral spread and reduce variant emergence. The heterologous scheme consisting of [...] Read more.

Background: With the emergence of SARS-CoV-2 Omicron sub-variants exhibiting increased transmissibility and immune escape, booster immunization is recommended. Ideally, vaccination across all age groups, including children and adolescents, is critical to control viral spread and reduce variant emergence. The heterologous scheme consisting of two doses of SOBERANA^® 02 followed by a third dose of SOBERANA^® Plus, which are recombinant protein subunit vaccines constructed from the ancestral RBD, has proven safety, immunogenicity, and effectiveness in pediatric populations as primary series. This study evaluated the safety and immunogenicity of a SOBERANA^® Plus booster dose administered six months after primary vaccination in individuals aged 3–18 years. Methods: In this follow-up analysis of a phase I/II trial, 244 participants received the booster. Safety was monitored via active surveillance at 1 h, 24 h, and over 28 days post-vaccination. Humoral responses were assessed 28 days post-booster. Antibody responses to the SARS-CoV-2 nucleocapsid (N) protein were assessed in all collected serum samples. Results: Adverse events occurred in 18% of participants, predominantly local (85.2%) versus systemic (14.8%); no serious or severe adverse events were reported. All humoral response parameters increased significantly post-booster, including neutralizing antibodies against D614G (24.7-fold increase) and Omicron BA.1 (55.9-fold increase), with similar responses in N-negative and N-positive individuals. Importantly, cross-neutralizing activity against recent Omicron sub-variants (XBB.1.5 and EG.5.1) was also detected. Conclusions: A SOBERANA^® Plus booster is safe and significantly enhances cross-neutralizing immunity against evolving Omicron sub-variants in children and adolescents. These results highlight the potential of first-generation RBD-based vaccines to maintain broad immunity despite viral evolution. Full article

(This article belongs to the Special Issue Human Immune Responses to Infection and Vaccination)

► Show Figures

Figure 1

12 pages, 14146 KB

Open AccessArticle

Disease and Economic Burden Averted by Hib Vaccination in 160 Countries: A Machine-Learning Analysis

by Dachuang Zhou, Siyang Chan, Yimei Zhong, Zhehong Xu, Jun Wang, Yuntian Wang, Yiyang Gao, Yuting Xia, Di Zhang and Wenxi Tang

Vaccines 2025, 13(12), 1197; https://doi.org/10.3390/vaccines13121197 - 27 Nov 2025

Abstract

Background: Global immunization against Haemophilus influenzae type b (Hib) has expanded with Gavi support. We estimated health, economic benefits, equity and cost-effectiveness in 159 countries (1990–2021), and projected effects of future introduction in China. Methods: We used a random forest model to simulate [...] Read more.

Background: Global immunization against Haemophilus influenzae type b (Hib) has expanded with Gavi support. We estimated health, economic benefits, equity and cost-effectiveness in 159 countries (1990–2021), and projected effects of future introduction in China. Methods: We used a random forest model to simulate counterfactual scenarios without Hib vaccine introduction in 159 countries (1990–2021) and to project effects of Hib vaccine introduction in China over the next decade. Ten variables were sourced from the World Bank and WHO; Hib disease burden estimates were from the Global Burden of Disease Study 2021. We compared counterfactual and actual results to quantify benefits, equity, and cost-effectiveness. Extensive uncertainty analyses were performed. Results: Between 1990 and 2021, Hib immunization averted an estimated 1,321,123 (95% uncertainty interval [UI] 32,034–2,723,304) deaths and 90,973,504 (95% UI 3,573,718–197,099,799) disability-adjusted life-years globally. Greatest health and economic gains occurred in Africa and low- and middle-income countries (LMICs). Deaths averted decreased with later vaccine introduction (Pearson’s r = −0.56). Vaccination did not improve health equity, and access remains limited in Africa and LMICs. Hib immunization was cost-saving in all countries. In China, introduction at any point in the next decade would provide health and economic benefits and be cost-effective, with earlier introduction yielding greater gains. Conclusions: Hib immunization provide substantial, cost-effective health and economic benefits globally. Persistent inequities in vaccine access for LMICs require targeted solutions. Policymakers in China should consider these findings for future vaccine introduction. Full article

(This article belongs to the Special Issue Promoting Research, Development and Access to Vaccines to Address Global Inequities)

► Show Figures

Figure 1

22 pages, 2308 KB

Open AccessArticle

A Rabies Virus Nucleocapsid-like Nanostructure Vaccine Based on Dual-Cationic Lipid Nanoparticles

by Zhixiao Zhang, Jingjing Zhang, Changyong Mu, Kaili Ma, Dongxiu Gao, Chang’e Liu, Lin Feng, Xiaowu Peng, Junbo Si, Hongbing Li, Yanrui Su, Fengyuan Zeng, Liping He, An Wang, Chongying Zhou, Zhenxiao Zhang, Yixuan Wang, Qiuqi Li, Jiahui Li, Shuiyan Zou, Miaomiao Xing, Huijuan Li, Meng Sun, Weijie Chang, Xiaoxia Yu, Junqing Li, Lichun Wang, Yanmei Li, Hongkun Yi, Lichun Zheng, Fuyun He and Qihan Li Show full author list Hide full author list

Vaccines 2025, 13(12), 1196; https://doi.org/10.3390/vaccines13121196 (registering DOI) - 26 Nov 2025

Abstract

Background: Rabies virus (RABV) causes approximately 59,000 human deaths annually. Current pre- and post-exposure vaccination relies on inactivated vaccines (INVs) with limited yield and immunogenicity. We engineered a dual-cationic LNP-based nucleocapsid-like nanostructure (NLS) that co-encapsulates RABV G-mRNA and recombinant RABV-N to engage MHC-I/II [...] Read more.

Background: Rabies virus (RABV) causes approximately 59,000 human deaths annually. Current pre- and post-exposure vaccination relies on inactivated vaccines (INVs) with limited yield and immunogenicity. We engineered a dual-cationic LNP-based nucleocapsid-like nanostructure (NLS) that co-encapsulates RABV G-mRNA and recombinant RABV-N to engage MHC-I/II pathways and enhance protection. Methods: A pVAX-RABV-G plasmid containing 5′/3′UTRs, Kozak, and poly(A) was transcribed in vitro. RABV-N with an N-terminal 6× His tag was expressed in E. coli BL21(DE3) and purified by Ni-Sepharose affinity chromatography. Dual-cationic LNPs (DHA, DOTAP Cl, mPEG-DTA2K, DOPC) were formulated by microfluidics at a 4:1 (G-mRNA:RABV-N) mass ratio. Vaccine quality was assessed by encapsulation efficiency, DLS, PDI, zeta potential, and TEM. Mice received empty LNPs, INV, G-mRNA, or NLS under varied schedules and doses. ELISA measured RABV-G/N-IgG; RFFIT determined neutralizing antibody (nAb) titers; ELISPOT quantified CTL response; qPCR assessed T-cell activation genes. On day 35 after the first immunization of vaccines, mice were challenged intramuscularly with 25 LD₅₀ of CVS-24. Results: G-mRNA purity was >95% and drove strong RABV-G expression in 293T cells. Purified RABV-N was approximately 52 kDa, >90% pure, and reactive to anti-His and anti-N antibodies. NLS achieved >95% encapsulation, a diameter of 136.9 nm, PDI 0.09, and a +18.7 mV zeta potential. A single dose yielded approximately 10 IU mL⁻¹ nAb by day 7; two doses peaked at approximately 1000 IU mL⁻¹. Mice showed 100% survival and no viral rebound in brain, spinal cord, and sciatic nerve. NLS induced stronger MHC-I/II-linked cellular immunity and higher RABV G/N-specific IFN-γ spot frequencies than G-mRNA or INV. Conclusions: The dual-antigen NLS vaccine co-delivering G-mRNA and RABV-N via dual-cationic LNPs robustly activates MHC-I/II, rapidly generates high-titer nAb (≥10 IU mL⁻¹ within 1 week), and sustains potent CD8⁺ CTL and CD4⁺ Th responses. A two-dose regimen (days 0 and 21) conferred complete protection, supporting the NLS platform as a next-generation rabies vaccine candidate. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

15 pages, 1227 KB

Open AccessArticle

Construction of a Full-Length Infectious Clone Derived from Type O Foot-and-Mouth Disease Virus Isolated in South Korea for Vaccine Development with High Antigen Productivity

by Jae Young Kim, Sun Young Park, Gyeongmin Lee, Sang Hyun Park, Jong Sook Jin, Jong-Hyeon Park and Young-Joon Ko

Vaccines 2025, 13(12), 1195; https://doi.org/10.3390/vaccines13121195 - 26 Nov 2025

Abstract

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals such as cattle and pigs, characterized by vesicular lesions in the mouth, nose, teats, and feet. Globally, the most commonly used FMD vaccines are inactivated vaccines produced by chemical inactivation [...] Read more.

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals such as cattle and pigs, characterized by vesicular lesions in the mouth, nose, teats, and feet. Globally, the most commonly used FMD vaccines are inactivated vaccines produced by chemical inactivation of the infectious FMD virus (FMDV). This study aimed to establish an infectious clone of the O/Boeun/SKR/2017 virus that has demonstrated the highest antigen productivity among the various type O vaccine strains developed in South Korea to date. Methods: An infectious clone was generated from a type O virus isolated during the 2017 FMD outbreak in South Korea. The viral genome was divided into two fragments, each amplified separately, and subsequently ligated to produce a full-length infectious clone. Results: Rescue of infectious FMDV was confirmed using a commercial antigen detection kit and electron microscopy. Under optimized culture conditions, the rescued virus titer reached 2 × 10⁷ TCID₅₀/mL, and the antigen yield was 6.4 µg/mL. Following inactivation, the antigen was formulated into a vaccine and administered to pigs. Four weeks post-vaccination, challenge with the live virus resulted in no clinical symptoms, demonstrating complete protective efficacy. Conclusions: To the best of our knowledge, this is the first report describing the construction of an infectious clone derived from a field FMDV isolate in South Korea and its application in vaccine development. The O/Boeun/SKR/2017 infectious clone may serve as a genetic backbone for the rapid generation of new FMD vaccine candidates with high antigen productivity by substituting epitopes from other FMDV. Full article

(This article belongs to the Section Veterinary Vaccines)

► Show Figures

Figure 1

14 pages, 381 KB

Open AccessArticle

Influencing Factors of Pregnant Women’s Willingness to Receive Influenza Vaccination in China

by Yi Tao, Nan Shan, Yan Wang, Minghong Sun, Lijuan Zhang, Lihong Yang, Lei Chen, Hongbo Qi and Junlong Li

Vaccines 2025, 13(12), 1194; https://doi.org/10.3390/vaccines13121194 - 26 Nov 2025

Abstract

Background: Seasonal influenza presents a major public health issue with a heavy disease burden on pregnant women, who are at increased risk of severe outcomes, yet vaccination uptake remains low. Objective: Investigate pregnant women’s willingness to receive influenza vaccination, identify key influencing factors, [...] Read more.

Background: Seasonal influenza presents a major public health issue with a heavy disease burden on pregnant women, who are at increased risk of severe outcomes, yet vaccination uptake remains low. Objective: Investigate pregnant women’s willingness to receive influenza vaccination, identify key influencing factors, and elucidate the pathways shaping this willingness. Methods: A cross-sectional web-based survey was performed. The questionnaire included their socioeconomic characteristics, pregnant status and histories, knowledge of the influenza vaccine, and attitudes toward the seasonal influenza vaccine. A univariate analysis was initially performed to screen potential variables associated with pregnant women’s willingness to receive influenza vaccination. Subsequently, a multivariate binary logistic regression model was constructed to assess the independent effects of these variables on vaccination willingness. Additionally, a mediation effect model was developed to analyze the mediating pathways of factors influencing vaccination willingness. Results: A total of 1231 pregnant women participated in this survey. Five hundred and seventy-one (46.4%) were willing to receive the seasonal influenza vaccine. Multivariate analysis identified five key factors influencing willingness: higher annual income (CNY ≥ 200,000 vs. ≤100,000: OR = 2.65, 95% CI: 1.02–6.85), history of delivery difficulties (OR = 0.10, 95% CI: 0.02–0.62), knowledge about the influenza vaccine (OR = 1.69, 95% CI: 1.28–2.23), supportive attitudes towards vaccination (OR = 13.35, 95% CI: 8.26–21.55), and willingness to pay over 500 yuan for the vaccine (OR = 2.29, 95% CI: 1.23–4.27). Attitudes towards vaccination were partially mediated by vaccine knowledge (β = 0.03, 16% of total effect), with no mediation effects observed for price or delivery history. Conclusions: This study pinpointed pivotal factors contributing to pregnant women’s hesitancy towards seasonal influenza vaccination. Our findings underscore the urgent need for integrating influenza vaccination programs with comprehensive educational and promotional strategies in the future. Full article

(This article belongs to the Section Influenza Virus Vaccines)

► Show Figures

Figure 1

14 pages, 258 KB

Open AccessArticle

Knowledge, Attitude, and Practices (KAP) About Vaccines Among Students in the Health Sciences Faculties in Kuwait

by Zahra K. Alsairafi, Abdallah Y. Naser, Abdullah N. Hasan, Ahmad Taqi, Mazen Ali and Sara Alsarraf

Vaccines 2025, 13(12), 1193; https://doi.org/10.3390/vaccines13121193 - 25 Nov 2025

Abstract

Background: Vaccination remains one of the most effective public health interventions, yet hesitancy persists even among healthcare students who aid in promoting immunization. Understanding students’ perspective plays a crucial role in designing targeted educational interventions. The purpose of this study was to evaluate [...] Read more.

Background: Vaccination remains one of the most effective public health interventions, yet hesitancy persists even among healthcare students who aid in promoting immunization. Understanding students’ perspective plays a crucial role in designing targeted educational interventions. The purpose of this study was to evaluate knowledge, attitude, and practices of healthcare students (HSCs) in Kuwait about vaccines. Methods: A quantitative, cross-sectional study was conducted between August and October 2024. A validated 21-item questionnaire was used to assess vaccine-related knowledge, attitude, and practices, along with demographic data. Descriptive statistics and binary logistic regression were used to identify predictors of higher knowledge and positive attitude. Results: A total of 351 students participated (mean age 23.0 ± 2.4 years; 90.6% female). The mean knowledge score was 3.9/7 (55.7%), indicating moderate knowledge, with misconceptions noted regarding benefits of post-infection vaccination and extra vaccine doses. The mean attitude score was 3.6/6 (60%), indicating moderately positive attitude, yet safety concerns, particularly about long-term effect, were common (59.3%). Nearly half (45.9%) delayed vaccination until mandatory. Vaccine uptake was highest for COVID-19 (92.3%), followed by hepatitis B (73.8%). Older age, male gender, and being a medical student predicted higher knowledge (p = 0.011), while older age and being in later study years predicted more positive attitude (p = 0.032). Conclusions: HSCs demonstrated moderate knowledge and attitude toward vaccines, with significant hesitancy driven by safety concerns despite high eventual uptake. Early targeted curricular interventions addressing vaccine safety evidence, benefits of timely immunization, and professional responsibility are warranted to improve confidence and proactive vaccine acceptance among future healthcare professionals (HCPs). Full article

(This article belongs to the Section Vaccines and Public Health)

26 pages, 5619 KB

Open AccessArticle

Identification of a Highly Potent Neutralizing Nanobody Against Human Adenovirus Type 4

by Tingting Yu, Wanrong Zhang, Peng Lv, Peijie Zhai, You Yang, Jianrong Wang, Zhengshan Chen, Guanying Zhang and Yunzhu Dong

Vaccines 2025, 13(12), 1192; https://doi.org/10.3390/vaccines13121192 - 25 Nov 2025

Abstract

Background: Human adenovirus type 4 (HAdV-4), the sole member of species Human mastadenovirus E (HAdV-E), is of zoonotic origin and has established stable human transmission through recombination, conferring distinctive host adaptation and pathogenicity. It causes respiratory and ocular diseases, with a significant risk [...] Read more.

Background: Human adenovirus type 4 (HAdV-4), the sole member of species Human mastadenovirus E (HAdV-E), is of zoonotic origin and has established stable human transmission through recombination, conferring distinctive host adaptation and pathogenicity. It causes respiratory and ocular diseases, with a significant risk of severe pneumonia in children. No targeted antivirals are approved for routine use, leaving supportive care as the primary management. China bears a relatively high HAdV-4 disease burden in Asia. Methods: To generate neutralizing nanobodies (Nbs) against HAdV-4, we employed an alpaca immunization strategy using hexon protein from Ad4-RI67 strain, followed by the isolation of hexon-specific nanobodies. The epitope competition and molecular docking was employed to analysis the binding site of the Nbs’. We engineered VHH-Fc fusions by conjugating VHH domains to human IgG1 Fc. The lead candidate, NVA17, showed efficacy in both in vitro and in vivo (Stat1^+/− mouse model). Flow cytometric analysis was employed to assess the downstream immune effects of NVA17 in vivo. Its intracellular neutralization mechanism was further investigated through confocal microscopy by examining co-localization in TRIM21-overexpressing and knockdown cells. Results: The isolated nanobodies revealed epitopes distinct from those targeted by known antibodies. The lead candidate NVA17 demonstrated potent neutralizing activity in vitro (IC₅₀ < 10 ng/mL). In the Stat1^+/− mouse model, NVA17 provided complete protection against lethal challenge, significantly reduced viral load in the lungs, and ameliorated pathological damage. NVA17 treatment dose-dependently reversed the virus-induced reduction in immune cell counts and enhanced cytotoxicity, suggesting a systemic immunomodulatory effect. Mechanistic studies indicated that the antiviral activity of NVA17 partly depends on the TRIM21-mediated antibody-dependent intracellular neutralization (ADIN) pathway, whereby TRIM21 terminates the viral life cycle by promoting viral degradation via K48-linked ubiquitination. Conclusions: We have identified multiple antibody candidates, particularly NVA17, with significant therapeutic potential for developing antibody-based treatments against HAdV-4. This offers a targeted intervention strategy to counter the current lack of specific antiviral therapies. Full article

(This article belongs to the Special Issue Recent Research on Adenovirus-Vectored Vaccines)

► Show Figures

Figure 1

18 pages, 1366 KB

Open AccessArticle

Factors Associated with Vaccination Status of Neonates in the Tertiary Referral Department of Neonatology and Neonatal Intensive Care in the North-Eastern Region of Poland

by Aleksander Kamianowski, Cezary Kamianowski, Gabriela Szpica, Angelika Jakubas, Anna Wasilewska and Monika Kamianowska

Vaccines 2025, 13(12), 1191; https://doi.org/10.3390/vaccines13121191 - 25 Nov 2025

Abstract

Introduction: Effective strategies to increase vaccination acceptance should be targeted to a given community. We decided to conduct a study analyzing the immunization status of neonates and factors influencing it in the Department of Neonatology and Neonatal Intensive Care of the Medical [...] Read more.

Introduction: Effective strategies to increase vaccination acceptance should be targeted to a given community. We decided to conduct a study analyzing the immunization status of neonates and factors influencing it in the Department of Neonatology and Neonatal Intensive Care of the Medical University of Bialystok, Poland. Material and Methods: The retrospective study was conducted between 2015 and 2024. Vaccinations against tuberculosis (Bacillus Calmette-Guérin (BCG) vaccine) and against hepatitis B (1st dose) were analyzed. The multivariate logistic regression was used to assess the relationship between immunization status and neonates’ characteristic. Results: 88.35% of the neonates (N = 18,643) received both vaccines. Of the 2459 unvaccinated neonates, 965 (39.24%) were due to parental refusal, with 720 (74.61% of this subgroup) refusing both vaccines. The fact that the neonate did not receive both vaccines was associated with the following variables: mother’s age (p = 0.004), place of residence (p = 0.012), parity (p = 0.002), and gestational age (p = 0.000). Conclusions: The analysis revealed a specific group of neonates who are at risk of not receiving both vaccines: term neonates born to multiparous mothers aged ≥35 years and living in cities. These results may suggest which patients, in particular, should be taken into account when designing strategies to increase vaccine acceptance in the area covered by the study. Full article

(This article belongs to the Section Vaccines and Public Health)

► Show Figures

Figure 1

12 pages, 405 KB

Open AccessArticle

The Safety and Immunogenicity of a 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine (CRM197/TT) in 12–23-Month Children: A Double-Blind, Randomized, Phase III Trial in China

by Zhiqiang Xie, Feiyu Wang, Lili Huang, Haitao Huang, Guangwei Feng, Xue Wang, Jiebing Tan, Xiaomin Ma, Wangyang You, Xiaolong Li, Jinbo Gou and Yanxia Wang

Vaccines 2025, 13(12), 1190; https://doi.org/10.3390/vaccines13121190 - 24 Nov 2025

Viewed by 122

Abstract

Objectives: This study systematically assessed the safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine (CRM197/TT, PCV13i) against the licensed PCV13 vaccine in a cohort of Chinese children between 12 and 23 months of age. Methods: This is a phase [...] Read more.

Objectives: This study systematically assessed the safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine (CRM197/TT, PCV13i) against the licensed PCV13 vaccine in a cohort of Chinese children between 12 and 23 months of age. Methods: This is a phase III, randomized, double-blind trial (NCT04841369). A total of 528 participants were randomized 1:1 to receive two doses of either PCV13i experimental or the PCV13 control vaccine at a 2-month interval, with 517 participants completing the vaccinations. Results: The overall incidence of adverse events (37.12% vs. 32.70%, p = 0.134) and adverse reactions (24.81% vs. 21.61%, p = 0.221) was comparable between the experimental and control groups. Local adverse reactions were more frequent in the experimental group (10.00% vs. 6.12%, p = 0.021), such as erythema (7.88% vs. 4.02%, p = 0.008). Systemic adverse reactions, including fever (10.77% vs. 13.77%), showed no significant differences. No vaccine-related serious adverse events occurred. Immunogenicity assessments showed that seropositivity rates for most serotypes reached ≥96% in both groups, with eight serotypes achieving 100% seropositivity in the experimental group. PCV13i induced higher IgG geometric mean concentrations (GMCs) for serotypes 3, 7F, and 19F (p < 0.05), whereas the control group showed higher GMCs for serotypes 1, 5, 6A, and 14 (p < 0.05). Opsonophagocytic activity (OPA)-related geometric mean titers (GMTs) were superior for PCV13i against serotypes 7F (39,583 vs. 17,249, p < 0.001) and 19F (1517 vs. 983, p = 0.028), but lower for serotype 5 (13 vs. 93, p < 0.001). Conclusions: PCV13i demonstrated non-inferior immunogenicity and an acceptable safety profile in 12–23-month-old children. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

► Show Figures

Figure 1

24 pages, 3742 KB

Open AccessArticle

Evaluation of a Cell-Adapted Live Attenuated African Swine Fever Virus Thai-Strain Vaccine Candidate: Highlighting Enhanced Virulence Risk in Co-Infected Pigs

by Challika Kaewborisuth, Theeradej Thaweerattanasinp, Nanchaya Wanasen, Apidsada Chorpunkul, Payuda Hansoongnern, Nathiphat Tanwattana, Kanjana Srisutthisamphan, Janya Saenboonrueng, Asawin Wanitchang, Suphot Wattanaphansak, Rachod Tantilertcharoen, Nattachai Suksawat, Jarin Kramyu, Benjamas Liwnaree, Papon Muangsanit, Kriangkrai Chaikhum, Tapanut Songkasupa, Thitawat Chanthaworn and Anan Jongkaewwattana

Vaccines 2025, 13(12), 1189; https://doi.org/10.3390/vaccines13121189 - 24 Nov 2025

Viewed by 86

Abstract

Background/Objectives: African swine fever (ASF) is a devastating disease affecting the swine industry globally. Development of safe and effective vaccines is an urgent need. This study aimed to evaluate, caASFV001-MA52, a cell-adapted ASFV strain derived from serial passaging in MA-104 cells, as a [...] Read more.

Background/Objectives: African swine fever (ASF) is a devastating disease affecting the swine industry globally. Development of safe and effective vaccines is an urgent need. This study aimed to evaluate, caASFV001-MA52, a cell-adapted ASFV strain derived from serial passaging in MA-104 cells, as a promising live-attenuated vaccine (LAV) candidate against virulent ASFV infection. Methods: Seven-week-old, crossbred pigs were immunized with caASFV001-MA52 (at a dose of 10⁵ TCID₅₀) and subsequently challenged with a lethal dose of virulent ASFV. Vaccine efficacy was measured through clinical monitoring, immunological and virological analyses, and pathological assessments of tissue protection and viral load reduction. Safety was critically assessed, particularly regarding its profile in animals with concurrent endemic porcine infections, including PCV, PRRSV and S. suis. Results: caASFV001-MA52 exhibits partial protection (70–80%) against the lethal challenge. Vaccinated and challenged survivors exhibited reduced viral loads and significantly alleviated pathological lesions compared to controls. Safety evaluations revealed that the vaccine’s profile is susceptible to concurrent infection. Pigs co-infected with endemic porcine pathogens showed increased virulence and mortality following vaccination. Although vaccination temporarily reactivated latent viral infections (PCV2, PCV3, and PRRSV), most surviving pigs effectively controlled and eliminated these co-infections. Conclusions: The caASFV001-MA52 strain demonstrates promising immunogenicity and protection against lethal challenges, supporting its continued development as an LAV candidate. However, the observed safety concerns regarding concurrent infections emphasize the critical need for veterinary health surveillance during its future practical application. Full article

(This article belongs to the Special Issue African Swine Fever Virus Vaccine Development)

► Show Figures

Figure 1

14 pages, 1220 KB

Open AccessArticle

Retrospective Analysis of HPV Vaccination Attitudes and Uptake Among Medical Students: Implications for Preventive Healthcare

by Sylwia Kałucka, Janusz Śmigielski, Agnieszka Głowacka, Paulina Oczoś and Izabela Grzegorczyk-Karolak

Vaccines 2025, 13(12), 1188; https://doi.org/10.3390/vaccines13121188 - 24 Nov 2025

Viewed by 106

Abstract

Background: Human papillomavirus (HPV) vaccination remains a critical preventive strategy against HPV-related cancers, yet uptake among young adults in Poland remains suboptimal. Objectives: This study aimed to assess HPV vaccination status, determinants, and perceived barriers to vaccination among healthcare students. Methods: This retrospective [...] Read more.

Background: Human papillomavirus (HPV) vaccination remains a critical preventive strategy against HPV-related cancers, yet uptake among young adults in Poland remains suboptimal. Objectives: This study aimed to assess HPV vaccination status, determinants, and perceived barriers to vaccination among healthcare students. Methods: This retrospective survey was conducted among 1062 students of the Medical University of Lodz, including those studying Medicine, Nursing, Midwifery, and Public Health. Results: Overall, 20% of respondents reported HPV vaccination, with the highest coverage among midwifery students (26.8%) and the lowest among medical students (16.8%). The major barriers to vaccination were found to be cost and misconceptions regarding vaccination age limits. As most respondents were above 14 years old when receiving the first dose, they were not eligible for the national free vaccination program. The significant motivators were parental influence and guidance from the medical university; however, recommendations for vaccination were infrequent. Multivariable logistic regression analysis found marital status (p = 0.029), paternal medical education (p = 0.003), and prior sexual experience (p = 0.037) to be significantly associated with vaccination status. Adverse events were reported by 45% of vaccinated respondents, most commonly reactions at the injection site. Nursing and midwifery students more often perceived adverse events as moderate or severe, but none discontinued vaccination. Conclusions: These findings underscore the need for financial support mechanisms and targeted educational interventions to enhance HPV vaccine uptake among future healthcare professionals in Poland. Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus (HPV) and Vaccination)

► Show Figures

Figure 1

22 pages, 2520 KB

Open AccessArticle

Antigen Format Determines Immunogenicity of AAV-Based SARS-CoV-2 Vaccines: Full-Length Spike Versus Truncated Subunits

by Anna V. Vakhrusheva, Maria E. Frolova and Arthur A. Isaev

Vaccines 2025, 13(12), 1187; https://doi.org/10.3390/vaccines13121187 - 24 Nov 2025

Viewed by 125

Abstract

Background: Antigen format strongly influences the immunogenicity of gene-based vaccines. Full-length Spike is widely used in licensed COVID-19 vaccines, while truncated subunits such as S1 or the receptor-binding domain (RBD) may simplify vector design but risk reduced potency. We aimed to compare these [...] Read more.

Background: Antigen format strongly influences the immunogenicity of gene-based vaccines. Full-length Spike is widely used in licensed COVID-19 vaccines, while truncated subunits such as S1 or the receptor-binding domain (RBD) may simplify vector design but risk reduced potency. We aimed to compare these antigen formats in an AAV9 delivery platform. Methods: BALB/c mice were immunized intramuscularly with recombinant AAV9 encoding full-length Spike, S1, or RBD at doses of 1 × 10¹⁰ or 1 × 10¹¹ viral genomes. Immune responses were assessed by serology, virus neutralization, T-cell profiling, and histopathology. Results: All constructs expressed antigen in vitro and in vivo. Only full-length Spike elicited robust neutralizing antibodies at both doses, with titers rising significantly by week 12. High-dose RBD induced neutralization in a minority of animals, whereas S1 failed to do so. Antigen-specific IgG responses scaled with insert length (Spike > S1 > RBD). Cellular immunity was dominated by CD8⁺ effector memory T cells, strongest in the Spike group, which also induced measurable CD4⁺ responses. Local transient myositis was observed at the injection site but resolved by week 24, with no systemic pathology. Conclusions: Full-length Spike outperforms truncated subunits in the AAV context, highlighting antigen structure as a critical factor for next-generation coronavirus vaccine design. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

► Show Figures

Figure 1

17 pages, 3216 KB

Open AccessArticle

The DNA Vaccines for the Gn and Gc Heterologous Polymer of Severe Fever with Thrombocytopenia Syndrome Virus Induce Potent Immunogenicity in Mice

by Qiuju He, Xiaojuan Liu, Jincheng Tong, Huan Li, Heng Zhang, Jiamin Chen, Mengyi Zhang, Zhihua Li and Qianqian Li

Vaccines 2025, 13(12), 1186; https://doi.org/10.3390/vaccines13121186 - 24 Nov 2025

Viewed by 105

Abstract

Introduction/Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a threat to global public health with a mortality rate of up to 30%. However, there is currently no commercialized SFTSV vaccine. This study focused on the construction of DNA vaccines with different structures [...] Read more.

Introduction/Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a threat to global public health with a mortality rate of up to 30%. However, there is currently no commercialized SFTSV vaccine. This study focused on the construction of DNA vaccines with different structures based on the surface glycoproteins Gn and Gc to identify the immunodominant conformations. Methods: The DNA vaccines encoding secretory proteins including Gn or Gc monomer, heterodimer of Gn and Gc (dimer), two forms of hexamer composed of the Gn and Gc heterodimer (hexamer-1 and hexamer-2) or ferritin nanoparticles of Gn, and non-secretory proteins including Gn (Gn-TM) and Gc (Gc-TM) were constructed. Western blot confirmed the expression level and the specificity of those DNA vaccines. After vaccinating mice with those DNA vaccines, its induced humoral and cellular immunity were comprehensively evaluated. Results: The DNA vaccines were constructed successfully. The DNA vaccines of Gn and polymers including dimer, hexamer-2, and ferritin nanoparticles inducing stronger binding antibody, neutralizing antibody, and antibody-dependent cellular cytotoxicity (ADCC) activity. The neutralizing antibody induced by these constructs was also cross-recognized by other five SFTSV pseudovirus strains. However, the T cell response induced by Gc, dimer or hexamer-2 DNA vaccines were significantly higher than those in most other groups, including Gn. Conclusion: The DNA vaccines encoding dimer or hexamer-2 demonstrated superior immunogenicity over other conformations, after taking the results of humoral and cellular responses into account. This study revealed the advantages of using polymer conformations in SFTSV vaccine design and provided new targets in SFTSV vaccine development. Full article

(This article belongs to the Special Issue The Development of Recombinant and Subunit Vaccines Against Infectious Diseases)

► Show Figures

Figure 1

11 pages, 672 KB

Open AccessArticle

COVID-19 Vaccination in Adults: Results from the Tanzania HIV Impact Survey 2022–2023

by Damian Jeremia Damian, Stephano G. Cosmas, Alice Wang, Magreth Kagashe, Aisha Haji, Jocelyn Rwehumbiza, Fahima Issa, Ahmed Khatib, Emilian Karugendo, Geofrey Mchau, Samuel Sumba, Rebecca Laws, Mary Mayige, Nicolas Schaad, Jerome Kamwela, Faki Faki, Deogratias Morice Kakiziba, Nyambura Moremi, Mahesh Swaminathan, Sarah Porter and Prosper Pendo Show full author list Hide full author list

Vaccines 2025, 13(12), 1185; https://doi.org/10.3390/vaccines13121185 - 24 Nov 2025

Viewed by 121

Abstract

Background: During the COVID-19 pandemic, vaccine hesitancy was high in Tanzania. Reasons for vaccine hesitancy included skepticism about vaccine safety and efficacy. Nonetheless, by March 2023, following concerted efforts, Tanzania reported reaching a national COVID-19 vaccination coverage of 52.5% among adults. We [...] Read more.

Background: During the COVID-19 pandemic, vaccine hesitancy was high in Tanzania. Reasons for vaccine hesitancy included skepticism about vaccine safety and efficacy. Nonetheless, by March 2023, following concerted efforts, Tanzania reported reaching a national COVID-19 vaccination coverage of 52.5% among adults. We analyzed COVID-19 vaccination status and perceived vaccine safety among adults aged ≥ 18 years using data from the Tanzania HIV Impact Survey (THIS) 2022–2023. Methods: The THIS 2022–2023 was a nationally representative, cross-sectional household survey with a stratified two-stage cluster design. Descriptive analyses were conducted to determine the proportion of adults who self-reported receiving the COVID-19 vaccine andcompleting the primary vaccine series, and to assess vaccine safety perceptions. Analyses were weighted for non-response and accounted for complex survey design. Results: Of 32,777 adults, 20.0% (95% confidence interval (CI): 18.9–21.1) reported receiving more than one COVID-19 vaccine dose. Of those, 82.9% (95% CI: 81.3–84.5) completed the primary vaccination series. The proportion of adults who reported vaccination increased with age from 12.5% among 18–24 year olds to 29.0% among those aged 55–64 years. Among adults living with HIV (ALHIV), 49.6% (95% CI: 47.1–52.1) were vaccinated, and vaccination rates increased with longer duration on antiretroviral therapy. Adults who perceived the vaccines as safe (27.9%, 95% CI: 26.4–29.3) were 10 times more likely to report being vaccinated than those who perceived the vaccines as “not at all safe” (2.7%, 95% CI: 2.0–3.6). Conclusions: The COVID-19 vaccination coverage in Tanzania among adults ≥ 18 years as measured through the THIS 2022–2023 was less than half the national COVID-19 vaccine coverage reported in March 2023. ALHIV were more likely than the general population to be vaccinated. The substantial difference in vaccination rates between those who perceived the vaccines as safe versus unsafe highlights the importance of safety perception for vaccine uptake. Full article

(This article belongs to the Section COVID-19 Vaccines and Vaccination)

► Show Figures

Figure 1

17 pages, 3922 KB

Open AccessArticle

Evolution and Vaccine Strain Match of HA and NA Genes of Influenza A/H3N2 Subtype in Riyadh, Saudi Arabia, 2020–2023

by Noorah A. Alkubaisi, Ibrahim M. Aziz, Mohamed A. Farrag, Reem M. Aljowaie, Asma N. Alsaleh, Fatimah N. Alanazi and Fahad N. Almajhdi

Vaccines 2025, 13(12), 1184; https://doi.org/10.3390/vaccines13121184 - 22 Nov 2025

Viewed by 464

Abstract

Background/Objectives: Although several studies have shed light on the epidemiology of the influenza A/H3N2 subtype in Saudi Arabia, the knowledge regarding the molecular epidemiology and genetic diversity of the A/H3N2 subtype in the Riyadh region is still significantly restricted. Thus, the current [...] Read more.

Background/Objectives: Although several studies have shed light on the epidemiology of the influenza A/H3N2 subtype in Saudi Arabia, the knowledge regarding the molecular epidemiology and genetic diversity of the A/H3N2 subtype in the Riyadh region is still significantly restricted. Thus, the current research intends to investigate the molecular epidemiology and circulation patterns of the influenza A/H3N2 subtype in Riyadh, Saudi Arabia, over the past 9 years. Methods: A total of 380 nasopharyngeal aspirate samples (NPAs) (winter seasons 2020–2023) were screened for the presence of A/H3N2 subtype. Results: Sixty-five samples (17.11%) were found to be positive for the influenza A virus (IAV). A/H3N2 subtype 35 (9.21%) slightly predominated over A/H1N1 pdm09 30 (7.89%), the incidence rate was high in males (16.47%), and the most affected group was the 0–4 age group (14, 14.75%). The phylogenetic analysis revealed that the majority of Riyadh A/H3N2 samples were categorized into the sub-clades 3c.2a1b.1a and 3c.2a1b.1b, which did not exhibit any exclusive clustering with the vaccine strains. Out of the 20 amino acid substitutions detected in the HA1 domain of A/H3N2 strains, 9 were not found in any of the vaccine strains. The HA protein from the Riyadh samples has 8–11 N-glycosylation sites, some of which have been recorded in vaccine strains, yet are lacking in all strains analyzed in this study. Conclusions: As a result, the flu vaccines administered in Saudi Arabia might need to be reevaluated to incorporate additional vaccine strains that are more pertinent to those currently circulating in the recent epidemic seasons in Saudi Arabia. Full article

(This article belongs to the Special Issue Influenza Virus Infections, Vaccines and Diagnosis)

► Show Figures

Figure 1

22 pages, 1635 KB

Open AccessReview

Self-Assembled Peptides: A New Generation of Vaccine Adjuvant Platform

by Miao-Miao Zhang, Ji Zhu, Zhao-Yi Wang, Yu-Lun Bai, Hai-Bo Li, Buhe Nashun and Yue Jiang

Vaccines 2025, 13(12), 1183; https://doi.org/10.3390/vaccines13121183 - 21 Nov 2025

Viewed by 659

Abstract

The advent of precision medicine has spotlighted subunit and peptide-based vaccines, which offer high safety but often require potent adjuvants to enhance immunogenicity. Self-assembled peptides have emerged as a promising adjuvant platform due to their ease of synthesis, excellent biocompatibility, and tunable structural [...] Read more.

The advent of precision medicine has spotlighted subunit and peptide-based vaccines, which offer high safety but often require potent adjuvants to enhance immunogenicity. Self-assembled peptides have emerged as a promising adjuvant platform due to their ease of synthesis, excellent biocompatibility, and tunable structural properties. Recent advances highlight their potential in boosting vaccine efficacy, with self-assembled peptides forming highly ordered architectures that are conducive to immune system activation. This review discusses the key factors driving peptide self-assembly and explores their evolving role as innovative vaccine adjuvants, alongside challenges and future development directions. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

► Show Figures

Figure 1

25 pages, 686 KB

Open AccessReview

Optimizing Humoral Immunity for Durable and Broad Protection in Flavivirus Vaccines

by Jae-Yeon Park and Hye-Mi Lee

Vaccines 2025, 13(12), 1182; https://doi.org/10.3390/vaccines13121182 - 21 Nov 2025

Viewed by 408

Abstract

Flavivirus infections, including dengue, Zika, West Nile, and Japanese encephalitis, remain a major global health concern. Although several vaccines are licensed, the durability and qualitative features of vaccine-induced antibodies differ substantially across platforms, leading to incomplete cross-protection and the risk of antibody-dependent enhancement. [...] Read more.

Flavivirus infections, including dengue, Zika, West Nile, and Japanese encephalitis, remain a major global health concern. Although several vaccines are licensed, the durability and qualitative features of vaccine-induced antibodies differ substantially across platforms, leading to incomplete cross-protection and the risk of antibody-dependent enhancement. Long-term durability is exemplified by YF-17D, which induces protective antibodies that have been detectable for decades, whereas the JE SA14-14-2 vaccine has achieved program-level reductions in disease in endemic regions. In contrast, CYD-TDV shows serostatus-dependent outcomes, and the investigational TAK-003 vaccine has demonstrated antibody persistence for at least four years. Recent studies have clarified how preserving quaternary envelope epitopes, minimizing prM-associated non-neutralizing specificity, and sustaining germinal center activity determine antibody affinity, breadth, and persistence. Advances in adjuvant formulations and delivery platforms have shown that engaging defined innate pathways and prolonging antigen availability enhance affinity maturation and long-lived plasma cell formation. Booster scheduling and baseline serostatus further shape the antibody quality, highlighting the importance of immune imprinting and cross-reactivity in vaccine design. Together, these findings outline the design principles for next-generation flavivirus vaccines, including stabilization of neutralization-sensitive epitopes, use of adjuvants that sustain germinal center responses, optimization of antigen persistence, and tailoring of dosing strategies to immune history to elicit durable and broadly protective humoral immunity. Full article

(This article belongs to the Special Issue Novel Vaccine Designs to Enhance the Engagement of Innate and Adaptive Immunity)

► Show Figures

Figure 1

13 pages, 402 KB

Open AccessArticle

Modeling Outbreak Prediction and the Impact of Emergency Vaccination on the 2024–2025 Chikungunya Outbreak in La Réunion

by Martijn Boer, Gerard Timmy Vondeling, Eric Plennevaux and Adrianne Marije de Roo

Vaccines 2025, 13(12), 1181; https://doi.org/10.3390/vaccines13121181 - 21 Nov 2025

Viewed by 241

Abstract

Background/Objectives: As of April 2025, La Réunion is facing a second major chikungunya virus (CHIKV) outbreak, following the 2005–2006 epidemic that infected nearly one-third of the population. IXCHIQ^®, a live-attenuated, single-dose vaccine, offers an opportunity for targeted immunization to complement vector [...] Read more.

Background/Objectives: As of April 2025, La Réunion is facing a second major chikungunya virus (CHIKV) outbreak, following the 2005–2006 epidemic that infected nearly one-third of the population. IXCHIQ^®, a live-attenuated, single-dose vaccine, offers an opportunity for targeted immunization to complement vector control efforts. Using surveillance data up to 23 February 2025 (week 7), we estimated the potential scale of the 2024–25 chikungunya outbreak in La Réunion and how much of the burden could have been averted by an emergency vaccination campaign at different detection thresholds. Methods: A stochastic SEIR–SEI host–vector model was calibrated to weekly case counts (weeks 46/2024–7/2025). We projected the epidemic under three vaccination-trigger scenarios (≥100, ≥3000, ≥40,000 detected cases) and two incremental vector-control assumptions (10% and 20% reductions in biting rate). Several mosquito-related parameters—extrinsic incubation period, offspring number, and mortality rate—were temperature-dependent, based on daily temperatures in La Réunion. Vaccination was applied homogeneously, using a 17% coverage to reflect the proportion of the population targeted in the initial public health recommendation. Results: Our findings indicate that without vaccination, up to 27.5% of the population could become infected. If vaccination would begin after 100 detected cases, 75% of infections could be prevented. Delaying until 3000 or 40,000 cases reduced effectiveness to 41% and 11%, respectively. Conclusions: Our results show that timely emergency vaccination can substantially reduce outbreak size. This underscores the importance of preparedness and rapid response by public health authorities in high-risk regions. Full article

(This article belongs to the Special Issue Vaccination Against Vector-Borne Diseases: Bridging Public Health and Epidemiology)

20 pages, 3047 KB

Open AccessArticle

Protective Efficacy of Two Novel DNA Vaccine Candidates Encoding TgGRA28 and TgGRA83 with an IL-28B Molecular Adjuvant Against Acute and Chronic Toxoplasmosis in Mice

by Jun Fang, Jingqi Mu, Rui Li and Jia Chen

Vaccines 2025, 13(12), 1180; https://doi.org/10.3390/vaccines13121180 - 21 Nov 2025

Viewed by 285

Abstract

Background: Toxoplasma gondii is a globally distributed apicomplexan parasite capable of causing congenital infections and spontaneous abortions in humans. While the parasite-secreted effector proteins TgGRA28 and TgGRA83 are known to mediate virulence or immune modulation, their potential as vaccine targets remains unexplored. Despite [...] Read more.

Background: Toxoplasma gondii is a globally distributed apicomplexan parasite capable of causing congenital infections and spontaneous abortions in humans. While the parasite-secreted effector proteins TgGRA28 and TgGRA83 are known to mediate virulence or immune modulation, their potential as vaccine targets remains unexplored. Despite its immunomodulatory properties, the role of IL-28B (a type III interferon) in enhancing DNA vaccine efficacy against T. gondii infection remains unclear. Methods: In this study, we constructed eukaryotic expression plasmids pVAX-GRA28, pVAX- GRA83 and pVAX-IL-28B. After transfection into -293-T cell, protein expression encoding TgGRA28 and TgGRA83 was confirmed via indirect immunofluorescence assay (IFA), while IL-28B expression was analyzed by ELISA. Subsequently, C57BL/6J or IFNαR1 knockout mice were immunized with single or dual-antigen DNA vaccines, with or without the molecular adjuvant pVAX-IL-28B. Immune responses were assessed through Toxoplasma-specific antibody levels, cytotoxic T lymphocyte (CTL) activity, cytokine profiling (IFN-γ, IL-2, IL-12p40, IL-12p70), and flow cytometric analysis of lymphocyte subsets and dendritic cells (DCs). Protective efficacy was determined by survival rates and brain cyst burden following challenge with 100 or 10 ME49 T. gondii cysts, respectively. Results: Vaccination with pVAX-GRA28 and pVAX-GRA83 elicited robust humoral immune responses with increased T. gondii-specific IgG levels and also Th1-polarized immunity, characterized by elevated IgG2a/IgG1 ratio, IFN-γ-dominant cytokine responses, and enhanced DCs, CD4+ and CD8+ T-cell activation. The cocktail vaccine conferred superior protection compared to single-antigen formulations, significantly improving survival and reducing cyst formation. Co-administration of pVAX-IL-28B further augmented vaccine-induced immunity, enhancing both cellular and humoral responses. Moreover, these DNA immunization with pVAX-GRA28 and pVAX-GRA83 plus pVAX-IL-28B induced robust protective immunity that was largely independent of type I IFN signaling, consistent with type III IFN biology. Conclusions: Our findings demonstrate that TgGRA28 and TgGRA83 are promising vaccine candidates against toxoplasmosis, capable of inducing protective immunity against acute and chronic infection. Moreover, IL-28B serves as a potent genetic adjuvant, warranting further investigation for its broader application in vaccines targeting apicomplexan parasites. Full article

(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)

► Show Figures

Figure 1

20 pages, 1242 KB

Open AccessReview

BCGitis and BCGosis: Clinical Spectrum, Immunological Mechanisms, and Risk Management

by Qibin Liu, Xiyong Dai and Shuang Wei

Vaccines 2025, 13(12), 1179; https://doi.org/10.3390/vaccines13121179 - 21 Nov 2025

Viewed by 368

Abstract

Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB), administered to >100 million neonates annually. It confers approximately 70–80% protection against tuberculous meningitis and miliary TB in early childhood, under-pinning its continued use in high-burden settings. As a live-attenuated vaccine, however, [...] Read more.

Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB), administered to >100 million neonates annually. It confers approximately 70–80% protection against tuberculous meningitis and miliary TB in early childhood, under-pinning its continued use in high-burden settings. As a live-attenuated vaccine, however, BCG can rarely cause adverse reactions ranging from self-limited local lesions to life-threatening disseminated BCG disease (BCGosis), which almost exclusively occurs in infants with severe primary or acquired immunodeficiencies such as SCID, MSMD, CGD, or symptomatic HIV infection. Implementation of universal newborn screening for severe combined immunodeficiency (SCID) using the T-cell receptor excision circle (TREC) assay now enables prospective identification and deferral of these high-risk neonates, virtually eliminating fatal BCGosis. Here we synthesize global data published since 2010 on the clinical spectrum, immunopathogenesis, and epidemiology of BCG-related complications, highlighting the impact of vaccine substrain, administration technique, and host immune status on adverse-event rates. On the basis of this evidence, we propose a practical, evidence-based risk-assessment checklist (BCG-RAKE) to support safer vaccine deployment while preserving the substantial TB-control benefits of universal BCG immunization. Full article

(This article belongs to the Special Issue Tuberculosis Diagnosis and Vaccines Research)

► Show Figures

Figure 1

14 pages, 264 KB

Open AccessArticle

Vaccine Hesitancy Toward Dengue Immunization Among Indonesian Office Workers: A Cross-Sectional Study of Perceptions, Barriers, and Trust Factors

by Theresia Santi, Ridwansyah Ridwansyah, Veli Sungono, Natalia Widjaya, Keinata Nabila Euqenekim, Cessya Prianyanta, Sri Rezeki S. Hadinegoro, Budi Setiabudiawan and Juandy Jo

Vaccines 2025, 13(12), 1178; https://doi.org/10.3390/vaccines13121178 - 21 Nov 2025

Viewed by 525

Abstract

Background/Objectives: In the absence of specific antiviral therapy for dengue viral infection, vaccination remains the most effective preventive measure. Two dengue vaccines have been licensed in Indonesia; however, concerns regarding vaccine hesitancy persist. This study aimed to assess dengue vaccine hesitancy among Indonesian [...] Read more.

Background/Objectives: In the absence of specific antiviral therapy for dengue viral infection, vaccination remains the most effective preventive measure. Two dengue vaccines have been licensed in Indonesia; however, concerns regarding vaccine hesitancy persist. This study aimed to assess dengue vaccine hesitancy among Indonesian office workers, comprising healthcare and non-healthcare workers. Methods: A cross-sectional study with an online survey was conducted between February 1 and April 30, 2025. Eligible participants were adults (≥18 years) employed in office-based settings, including healthcare facilities. Questionnaires were disseminated through company management teams and included 37 items on demographic characteristics, vaccination intentions, and underlying motivations. Data were analyzed to identify determinants of vaccine hesitancy. Results: A total of 377 respondents participated, the majority of whom were from West Java (335; 88.9%). One-third of respondents reported uncertainty regarding dengue vaccination (33.4% “not sure”), which was paralleled by hesitancy to pay for vaccination (43.2% “not sure”). Multivariable logistic regression analysis identified five significant determinants of vaccine hesitancy, with willingness-to-pay emerging as the strongest factor (β coefficient = 2.024; OR = 7.57; 95% CI = 4.06–14.10; p-value < 0.01). Conclusions: Approximately one-third of the surveyed Indonesian office workers exhibited hesitancy toward dengue vaccination. Willingness-to-pay was the most influential determinant of vaccine acceptance. Targeted strategies to address financial concerns and improve confidence in dengue vaccination are essential for strengthening workforce protection and national preparedness against dengue outbreaks. Full article

(This article belongs to the Special Issue Global Immunization Inequities-Challenges and Solutions)

21 pages, 1896 KB

Open AccessArticle

Adenoviral Vectors Expressing Optimized preM/E Genes of WNV Deliver Long-Term Protection Against Lethal West Nile Virus Challenge

by Tatiana A. Ozharovskaia, Olga V. Zubkova, Elizaveta V. Korobova, Inna V. Dolzhikova, Denis I. Zrelkin, Olga Popova, Polina P. Goldovskaya, Anna V. Kovyrshina, Anastasia I. Korobkova, Irina A. Favorskaya, Irina V. Vavilova, Daria M. Grousova, Ilya D. Zorkov, Anna A. Iliukhina, Irina A. Ermolova, Amir I. Tukhvatulin, Dmitry N. Shcherbinin, Ekaterina I. Ermolova, Marina S. Kunda, Natalia N. Ryzhova, Olga L. Voronina, Alexander S. Semikhin, Dmitry V. Shcheblyakov, Denis Y. Logunov and Alexander L. Gintsburg Show full author list Hide full author list

Vaccines 2025, 13(12), 1177; https://doi.org/10.3390/vaccines13121177 - 21 Nov 2025

Viewed by 345

Abstract

Background/Objectives: Flaviviruses, including West Nile virus (WNV), pose global health challenges due to their worldwide distribution, pathogenicity, and lack of effective treatments or vaccines. Today, WNV is considered the most important causative agent of viral encephalitis worldwide. This study investigated the different [...] Read more.

Background/Objectives: Flaviviruses, including West Nile virus (WNV), pose global health challenges due to their worldwide distribution, pathogenicity, and lack of effective treatments or vaccines. Today, WNV is considered the most important causative agent of viral encephalitis worldwide. This study investigated the different forms of the main WNV antigen—the preM/E protein—in the context of its immunogenic and protective properties. Methods: The recombinant adenovirus type 2 (rAd2) vectors expressing different forms of the WNV preM/E genes were obtained using standard molecular biology techniques. Immunogenicity in mice was assessed by enzyme-linked immunosorbent assay (ELISA) and virus neutralization assay. Immunological efficacy was evaluated in a mouse viral challenge model. Results: The rAd2 vector expressing the West Nile virus preM/E gene with mutations in the fusion loop exhibited robust immunogenicity when administered intramuscularly either once or in a homologous prime-boost regimen. This antigen form, as part of an adenoviral vector, protected mice from death in viral challenge experiments, providing 100% survival following WNV challenge. Conclusions: We believe that a vaccination strategy involving a recombinant adenoviral vector based on human adenovirus type 2 and the WNV antigen represented by the preM/E gene with mutations in the fusion loop may be a promising approach for combating West Nile virus infection. Full article

(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)

► Show Figures

Figure 1

13 pages, 951 KB

Open AccessArticle

A Novel, Safe, Non-Adjuvanted Alphavirus RNA Particle Vaccine Expressing the Rabies Virus Glycoprotein Induces a Three-Year Duration of Immunity in Dogs and Cats After a Single Vaccine Dose

by Ken Stachura, Randall Davis, Kari Carritt, Mark Mogler, Zach Xu and Ian Tarpey

Vaccines 2025, 13(12), 1176; https://doi.org/10.3390/vaccines13121176 - 21 Nov 2025

Viewed by 343

Abstract

Background/Objectives: To this day, rabies remains a significant global threat. This threat remains even with the availability of vaccines for humans, wildlife, and domestic animals, which are used as part of a series of interventions to attempt to control the infection and disease. [...] Read more.

Background/Objectives: To this day, rabies remains a significant global threat. This threat remains even with the availability of vaccines for humans, wildlife, and domestic animals, which are used as part of a series of interventions to attempt to control the infection and disease. The number of annual human deaths from rabies globally remains significant, with infections being mainly caused by domestic dogs. Although a number of vaccines exist for domestic animals, most contain inactivated rabies virus with adjuvants. Methods: To investigate alternatives to conventional rabies vaccines for dogs and cats, we developed a novel, non-adjuvanted, low-volume (0.5 mL) vaccine, based on the Venezuelan equine encephalitis virus (VEEV) TC-83-derived RNA particle (RP) expressing the rabies glycoprotein (G). This novel vaccine combines the safety profile of a non-adjuvanted vaccine while inducing consistently high efficacy and an extended duration of immunity similar to that shown by adjuvanted vaccines. Results: In multiple studies, we demonstrated that young kittens and puppies can be safely vaccinated without serious adverse effects. In graded dose experiments with cats and dogs, the RNA particle vaccine induced neutralizing levels of antibodies. Additionally, in vaccination/challenge studies, 100% protection from virulent rabies was demonstrated in excess of three years post-vaccination from a single dose at 12 weeks of age in both dogs and cats. The safety of the RP-Rabies vaccine in dogs and cats as young as twelve weeks of age was demonstrated in field safety studies using two vaccine serials formulated at a field dose. Conclusions: Data from these studies suggest that the RP-Rabies vaccine offers an excellent alternative to current vaccines combining the safety of a non-adjuvanted vaccine in a low-volume, single dose with the induction of an extended duration of immunity of at least three years in both dogs and cats. Full article

(This article belongs to the Special Issue Advances in Rabies Vaccination)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Vaccines, Volume 13, Issue 12 (December 2025) – 24 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI